PROJECT SUMMARY: The unique susceptibility of pregnant women to influenza virus infection, as well as the ability of maternally-derived immunity to provide fetal/neonatal protection has increased attention to maternal immunization. However, influenza vaccine coverage has been historically lower than expected in this population. Currently, data on influenza vaccine safety and efficacy during pregnancy are inadequate, which could be one of the main reasons for lower vaccination coverage in pregnant women. Initial assessment of the risk-benefit of maternal vaccination in prevention of viral infection requires a comparable animal model. This proposed study will establish a pregnant sow model to evaluate the safety and efficacy of a candidate influenza vaccine during pregnancy. In our previous studies supported by NIH (1R15A1090582), we generated a candidate influenza vaccine (TX98-129), which expresses a chimeric HA derived from HAs of four genetically distinct swine influenza A viruses (H1N1) that had history of zoonotic transmission. In this proposed study, we will perform in vivo evaluation of the candidate TX98-129 vaccine in pregnant sows. Our research team will recruit highly motivated pre-veterinary undergraduate students to participate in the project, in which students will receive broad training in vaccinology and animal model systems. Specific Aims are: 1) To assess the safety and efficacy of the candidate influenza vaccine in pregnant sows and fetal development; 2) To determine the effect of vaccine-induced maternal passive immunity on protecting neonatal pigs from influenza virus infection; 3) To integrate pre-veterinary undergraduate students into the research. Outcomes of this study will provide comparative information on the effect of our candidate influenza vaccine on maternal immunity and fetal development. The pregnant sow/fetus model will be a highly comparative system for future evaluating the effect of vaccines, therapeutic drugs and other treatments on prevention of viral infection during pregnancy, as well as to study their impact on human fetal development and consequences. In addition, the collaborative research environment created in this project will provide multidisciplinary training opportunities for undergraduate students.